Medical research is rapidly discovering therapeutic applications for nitric oxide (NO), a simple diatomic signaling molecule, including fields of vascular surgery and interventional cardiology. It has been known for some time now that NO is a signaling molecule with properties such as anti-inflammation, anti-restenosis, vasodilatation and promotion of endothelization. Recently, however, NO has been shown to significantly reduce thrombocyte aggregation and adhesion. Thrombocyte aggregation occurs within minutes following the initial vascular insult and once the cascade of events leading to restenosis is initiated, irreparable damage can result. Moreover, the risk of thrombogenesis and restenosis persists until the endothelium lining the vessel lumen has been repaired. Therefore, it is essential that NO, or any anti-restenotic agent, reach the injury site immediately.
One approach for providing a therapeutic level of NO at an injury site is to increase systemic NO levels prophylactically. This can be accomplished by stimulating endogenous NO production or using exogenous NO sources. Exogenous NO sources such as pure NO gas are highly toxic, short-lived and relatively insoluble in physiological fluids. Consequently, systemic exogenous NO delivery is generally accomplished using organic nitrate prodrugs such as nitroglycerin tablets, intravenous suspensions, sprays and transdermal patches. The human body rapidly converts nitroglycerin into NO; however, enzyme levels and co-factors required to activate the prodrug are rapidly depleted, resulting in drug tolerance. Moreover, systemic NO administration can have devastating side effects including hypotension and free radical cell damage. Therefore, using organic nitrate prodrugs to maintain systemic anti-restenotic therapeutic blood levels is not currently possible.
Therefore, considerable attention has been focused on localized, or site specific, NO delivery to ameliorate the disadvantages associated with systemic prophylaxis. Implantable medical devices coated with NO-releasing compounds have been evaluated. Implantable medical device coatings or substances used as medical devices need to be biocompatible yet function as a reservoir for the bioactive agent and sustain an appropriate controlled release of the bioactive agent.
Poly(tetrafluoroethylene) (PTFE) is widely used in implantable medical devices, in conjunction with a medical device or as a device itself. PTFE as an implantable material generally shows biocompatibility. However, as with any implantable material, there are continued efforts to improve the biocompatibility of PTFE through surface engineering. One common surface engineering procedure involves the introduction of poly(ethylene glycol) groups on the surface. This procedure adds hydrophilicity to the material, thereby increasing its biocompatibility.
Consequently, an implantable material such as PTFE with an engineered surface with increased biocompatibility coupled with the local delivery of NO may prove to be beneficial. The present disclosure attempts to fulfill this shortcoming by providing modified PTFE surfaces which can bind and controllably release NO to the surrounding tissues.